Foreign trade is an important part of the national economy. Promoting the development of foreign trade can regulate the optimal allocation of resources, raise the level of domestic productivity, and accelerate economic development. As a traditional inland agricultural province, Henan Province has inherent disadvantages in developing foreign trade due to its geographical location. However, it has characteristic advantages in terms of population and transportation, so it is necessary to study the pattern of foreign trade and the factors affecting it in this region. In this research study, statistical data were assessed with methods such as the foreign trade dependence, geographical detector, and gravity models to analyze the trade scale, pattern, spatio-temporal variation characteristics, and foreign trade mechanisms in Henan Province. The results show that the trade pattern of Henan Province from 2002 to 2021 has evident spatial and temporal heterogeneity, with a relatively homogeneous overall commodity structure, weak competitive advantages, and a high degree of dependence on US trade. Innovation and transportation are essential internal factors, while the external factors are positively affected by the GDP of both Henan Province and the trading countries, FTAs, trade openness, and the population in the long run and are negatively impacted by distance. This study provides suggestions and decision support for formulating foreign trade policies for Henan Province. It also provides a research basis for related corresponding studies of other regions with similar characteristics.